2025-524312-11-00招募中3 期
Everolimus bAsed caLcineurin inhibiTor frEe immunosuppRession oNe year AfTer lIver transplantatiON (ALTERNATION) – a randomized, prospective, multicenter, open-label, controlled phase III trial
Medizinische Hochschule Hannover32 个研究点 分布在 1 个国家目标入组 150 人开始时间: 2026年6月15日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 32
- 主要终点
- Change in estimated glomerular filtration rate (eGFR (ml/min)) from baseline to 14 months after randomization – eGFR will be calculated using the CKD-EPI Creatinine equation according to the national kidney foundation, 2021.(1)
研究概览
简要总结
The primary objective is to demonstrate that Calcineurin-inhibitor (CNI)-free immunosuppression (IS) is superior in sparing kidney function (measured as change from baseline to 14 months in estimated glomerular filtration rate (eGFR)) beyond year one after liver transplantation compared to standard therapy with CNI-based IS regimen in liver allograft recipients without relevant subclinical graft injury.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Men**, women* (biological sex), aged ≥ 18 or <80 years; *Women without childbearing potential defined as follows: • at least 6 weeks after surgical sterilization by salpingectomy or bilateral oophorectomy or • hysterectomy or uterine agenesis or • ≥ 50 years and in postmenopausal state > 1 year or • < 50 years and in postmenopausal state > 1 year with serum FSH > 40 IU/l and serum estrogen < 30 ng/l or a negative estrogen test, both at screening or *Women of childbearing potential: • Must have a negative pregnancy test at screening with a sensitivity of at least 25 mIU/ml. A repeat negative pregnancy test is required immediately prior to treatment initiation at baseline to confirm non-pregnancy status. • Must agree to undergo additional pregnancy testing as specified in section 6.2, or when clinically indicated (e.g., following a reported contraceptive failure). • Must agree to use at least one highly effective method of contraception (as defined in section 3.2.1) from the time of screening until 8 weeks after completion of studytreatment. • For participants using hormonal contraception, a barrier method (preferably a male condom) must be used in addition to the primary method from screening until 8 weeks after the end of treatment, to minimize the risk of reduced contraceptive efficacy **Sexually active and fertile male study subjects • Must use a condom from screening, during treatment with mycophenolate mofetil (MMF) and for at least 90 days after discontinuation of treatment. • If the male participant has a female partner of childbearing potential who is not pregnant, additional contraceptive measures should be considered for the partner. • The requirement for condom use may be waived provided that a highly effective method of contraception is consistently used by the female partner of childbearing potential.
- •Signed written informed consent from subject
- •Liver allograft recipients, either deceased or living donor liver transplant
- •Liver transplantation more than 12 months ago and less than 36 months ago
- •Recipients of single organ transplant only
- •Liver Transplant Recipient (LTR) on CNI-based maintenance IS
- •Liver enzymes: alanine aminotransferase (ALT) < 2x upper limit of normal (ULN) and ALP < 2xULN
排除标准
- •Previous CNI-free IS
- •Need for chronic anti-coagulation that cannot be safely discontinued to perform a liver biopsy
- •Inability to participate in frequent monitoring of liver function (every 8 weeks) and clinical visits during the trial duration (38 months)
- •Malignancy or active infection including active, replicative viral hepatitis (chronic hepatitis does not belong to exclusion criteria)
- •Recurrence of underlying liver disease
- •Subjects who are pregnant or breastfeeding
- •The use of any prohibited medication specified in section 5.2 is not permitted, unless the patient can be safely transitioned to an alternative medication at least 5 half-lives prior to the start of study-specific treatment (baseline).
- •Hypersensitivity or intolerance to any of the components of the medications used
- •Participation in another clinical trial (other investigational drugs or devices at the time of enrolment or within 30 days prior enrolment or within five half-lives of the IMP, whichever is longer)
- •Any medical condition which could compromise participation in the study according to the investigator’s assessment.
- •Accommodation in an institution pursuant to a court or administrative order
- •Histological exclusion criteria in the baseline screening biopsy: a. more than mild portal tract inflammation, presence of interface hepatitis, more than mild lobular inflammation b. presence of biliary inflammation, endothelialitis, portal microvasculitis, central perivenulitis c. advanced fibrosis (≥2 in any scale of LAF score) d. evidence of acute or chronic rejection (T cellmediated or antibody-mediated, plasma-cell-rich, chronic ductopenic rejection)
- •Acute or chronic rejection within the 36 months prior to screening
- •Prednisolone intake due to another autoimmune disease for no longer than 8 weeks
- •eGFR <30ml/min and/or proteinuria >0.5g/l (to mitigate the risk of worsening renal failure should rejection occur and high level of CNI might be required and proteinuria as a contraindication for mTORI-based therapy)
研究组 & 干预措施
CICLOSPORIN
Test
干预措施: CICLOSPORIN (Drug)
MYCOPHENOLATE MOFETIL
Test
干预措施: MYCOPHENOLATE MOFETIL (Drug)
EVEROLIMUS
Test
干预措施: EVEROLIMUS (Drug)
TACROLIMUS
Test
干预措施: TACROLIMUS (Drug)
结局指标
主要结局
Change in estimated glomerular filtration rate (eGFR (ml/min)) from baseline to 14 months after randomization – eGFR will be calculated using the CKD-EPI Creatinine equation according to the national kidney foundation, 2021.(1)
Change in estimated glomerular filtration rate (eGFR (ml/min)) from baseline to 14 months after randomization – eGFR will be calculated using the CKD-EPI Creatinine equation according to the national kidney foundation, 2021.(1)
次要结局
- Biopsy-proven acute liver graft rejection or liver graft loss (whichever occurs first) until month 14. Biopsy proven acute rejection (BPAR) (yes/no) is defined as liver enzyme elevation above 2xULN and histological criteria according to the most recent BANFF consensus.(2)
- Change in estimated glomerular filtration rate (eGFR (ml/min)) from baseline to end of follow-up (38 months)
- Biopsy- proven acute liver graft rejection or liver graft loss (whichever occurs first) until month 38
- Progression of chronic kidney disease to stage 4, 5 or requirement for renal replacement therapy (yes/no)
- Incidence of liver-related mortality (yes/no)
- Progression of subclinical graft injury (fibrosis) at rebiopsy at month 14 and end of follow-up, where progression in the svLBx is defined as reaching histological exclusion criteria from baseline biopsy (≥ 2 points)
- Progression of subclinical inflammation at rebiopsy at month 14 (yes/no) and end of follow-up (yes/no), where inflammation in the svLBx is defined as reaching exclusion criteria from baseline biopsy (≥ 2 points in any subscore)
- Quality of life: change from baseline to months 14 and end of follow-up (measured with PROMIS and SF-36)
- De novo development of donor specific HLA antibodies (yes/no)
- Increase in liver stiffness above 8,4 kPa (yes/no)
- Incidence of malignancy (yes/no)
- Occurrence of infections requiring medical intervention or hospitalization (yes/no)
- New onset of comorbidities including hypertension (yes/no), dyslipoproteinemia (yes/no) and diabetes mellitus (yes/no)
研究者
Klinik für Gastroenterologie, Hepatologie, Infektiologie und Endokrinologie
Scientific
Medizinische Hochschule Hannover
研究点 (32)
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